Ranitidine (V) and nizatidine (VI) are extremely potent histamine H.sub.2 -receptor antagonists. They are used as effective drugs in peptic ulcers and associated gastrointestinal disorders.
The synthesis of Ranitidine (V) involves condensation of 1-methylamino-1-methylthio-2-nitroethene (II) and 2-(((5-(dimethylamino) methyl-2-furanyl)methyl)thio) ethanamine (VII) (Spanish Patent ES No. 501,844 (1982); Spanish Patent ES No. 502,940 (1982). In another approach for ranitidine (V), 1-methylamino-1-methylthio-2-nitroethene (II) is reacted with ethylenimine and the product so obtained is condensed with ((5-(dimethylamino)methyl-2-furanyl)-methyl mercaptan (VIII) (Belgium Patent Application BE No. 888,747 (1981); Spanish Patent ES No. 529,532 (1986).
In the prior art, the preparation of 1-methylamino-1-methylthio-2-nitroethene (II) involves amination of sulfoxide III. German Offen No. 2,621,092 (1976), for example, describes the preparation of II by the reaction of methylamine with sulfoxide III. European Patent EP No. 58,492 (1982) and Belgium Patent Application BE No. 888,747 (1981) describe the preparation of 1-methylamino-1-methylthio-2-nitroethene (II) by amination of 1,1-bismethylthio-2-nitroethene (IV) with methylamine.
In all the above processes, constituting the prior art, methylamine is reacted with the substrates (III) or (IV). In this reaction, the high nucleophilicity of methylamine results in the rapid reaction of the required product (II) with a second molecule of methylamine. This unwanted reaction results in the formation of the by-product 1,1-bismethylamino-2-nitroethene (IX). EQU (CH.sub.3 NH).sub.2 C.dbd.CHNO.sub.2 IX
The removal of this from the required product (II) poses problems in purification and consequently the yield is reduced. In the prior art process, this problem is sought to be overcome by stopping the reaction at below 50% conversion. This involves recovery and recycling of starting material thereby increasing the number of operations.